Algae are an entry point for mercury (Hg) into the food web. Bioconcentration of Hg by algae is crucial for its biogeochemical cycling and environmental risk. Herein, considering the cell heterogeneity, we investigated the bioconcentration of coexisting isotope-labeled inorganic (199IHg) and methyl Hg (201MeHg) by six typical freshwater and marine algae using dual-mass single-cell inductively coupled plasma mass spectrometry (scICP-MS). First, a universal pretreatment procedure for the scICP-MS analysis of algae was developed. Using the proposed method, the intra- and interspecies heterogeneities and the kinetics of Hg bioconcentration by algae were revealed at the single-cell level. The heterogeneity in the cellular Hg contents is largely related to cell size. The bioconcentration process reached a dynamic equilibrium involving influx/adsorption and efflux/desorption within hours. Algal density is a key factor affecting the distribution of Hg between algae and ambient water. Cellular Hg contents were negatively correlated with algal density, whereas the volume concentration factors almost remained constant. Accordingly, we developed a model based on single-cell analysis that well describes the density-driven effects of Hg bioconcentration by algae. From a novel single-cell perspective, the findings improve our understanding of algal bioconcentration governed by various biological and environmental factors.
Mercury , Mercury/metabolism , Mass Spectrometry , Methylmercury Compounds/metabolism , Water Pollutants, Chemical/metabolism , Food Chain , Single-Cell Analysis
BACKGROUND: The prognosis of patients with thalamic hemorrhage is poor, and their long-term neurological impairment is heavy, which seriously affects their work and life.To comparatively analyse the efficacy and prognosis of patients with moderate hemorrhage in the thalamic region who underwent conservative treatment, stereotactic puncture surgery and neuroendoscopic surgery. METHOD: This study retrospectively analyzed hospitalization data from 139 adult patients with moderate-volume cerebral hemorrhage in the thalamo-endocapsular region. They were categorized into a stereotactic group (39cases), a neuroendoscopic group (36cases), and a conventional conservative group (64cases). Logistic regression analysis was used to assess risk factors for severe neurological deficits in patients. Multivariate regression modeling was used to compare the correlation of severe neurological deficits among the three groups of patients. RESULTS: Patients with thalamic moderate-volume cerebral hemorrhage had statistically significantly higher Assessment of Daily Living (ADL) scores in the stereotactic surgery group than in the conservative treatment group and the neuroendoscopic surgery group after 6 months of treatment (p< 0.001).The amount of residual hematoma was significantly lower in the surgery groups than in the conservative treatment group at 3 days, 7 days, and 2 weeks after the onset of the disease (P< 0.001).In multivariate logistic regression analyses, after adjusting for all covariates, the odds ratios for severe neurologic dysfunction in the stereotactic group and the neuroendoscopy group were, respectively, OR: 0.37 (0.12-0.87), P< 0.001 and 0.42 (0.23-1.13), P=0.361). CONCLUSION: In patients with moderate volume cerebral hemorrhage in the thalamus-inner capsule region cerebral hemorrhage, patients treated with stereotactic surgery combined with early hyperbaric oxygen therapy may have better long-term neurological recovery compared with conservative and neuroendoscopic surgical treatments.
Hg(I) may control Hg redox kinetics; however, its metastable nature hinders analysis. Herein, the stability of Hg(I) during standard preparation and analysis was studied. Gravimetric analysis showed that Hg(I) was stable in its stock solution (1000 mg L-1), yet completely disproportionated when its dilute solution (10 µg L-1) was analyzed using liquid chromatography (LC)-ICPMS. The Hg(I) dimer can form through an energetically favorable comproportionation between Hg(0) and Hg(II), as supported by density functional theory calculation and traced by the rapid isotope exchange between 199Hg(0)aq and 202Hg(II). However, the separation of Hg(0) and Hg(II) (e.g., LC process) triggered its further disproportionation. Polypropylene container, increasing headspace, decreasing pH, and increasing dissolved oxygen significantly enhanced the disproportionation or redox transformations of Hg(I). Thus, using a glass container without headspace and maintaining a slightly alkaline solution are recommended for the dilute Hg(I) stabilization. Notably, we detected elevated concentrations of Hg(I) (4.4-6.1 µg L-1) in creek waters from a heavily Hg-polluted area, accounting for 54-70% of total dissolved Hg. We also verified the reductive formation of Hg(I) in Hg(II)-spiked environmental water samples, where Hg(I) can stably exist in aquatic environments for at least 24 h, especially in seawater. These findings provide mechanistic insights into the transformation of Hg(I), which are indicative of its further environmental identification.
Mercury , Water Pollutants, Chemical , Mercury/analysis , Seawater/analysis , Seawater/chemistry , Isotopes/analysis , Water Pollutants, Chemical/analysis
In the continuous cropping of Panax notoginseng, the pathogenic fungi in the rhizosphere soil increased and infected the roots of Panax notoginseng, resulting in a decrease in yield. This is an urgent problem that needs to be solved in order to effectively overcome the obstacles associated with the continuous cropping of Panax notoginseng. Previous studies have shown that Bacillus subtilis inhibits pathogenic fungi in the rhizosphere of Panax notoginseng, but the inhibitory effect was not stable. Therefore, we hope to introduce biochar to help Bacillus subtilis colonize in soil. In the experiment, fields planted with Panax notoginseng for 5 years were renovated, and biochar was mixed in at the same time. The applied amount of biochar was set to four levels (B0, 10 kg·hm-2; B1, 80 kg·hm-2; B2, 110 kg·hm-2; B3, 140 kg·hm-2), and Bacillus subtilis biological agent was set to three levels (C1, 10 kg·hm-2; C2, 15 kg·hm-2; C3, 25 kg·hm-2). The full combination experiment and a blank control group (CK) were used. The experimental results show that the overall Ascomycota decreased by 0.86%~65.68% at the phylum level. Basidiomycota increased by -73.81%~138.47%, and Mortierellomycota increased by -51.27%~403.20%. At the genus level, Mortierella increased by -10.29%~855.44%, Fusarium decreased by 35.02%~86.79%, and Ilyonectria increased by -93.60%~680.62%. Fusarium mainly causes acute bacterial wilt root rot, while Ilyonectria mainly causes yellow rot. Under different treatments, the Shannon index increased by -6.77%~62.18%, the Chao1 index increased by -12.07%~95.77%, the Simpson index increased by -7.31%~14.98%, and the ACE index increased by -11.75%~96.12%. The good_coverage indices were all above 0.99. The results of a random forest analysis indicated that Ilyonectria, Pyrenochaeta, and Xenopolyscytalum were the top three most important species in the soil, with MeanDecreaseGini values of 2.70, 2.50, and 2.45, respectively. Fusarium, the primary pathogen of Panax notoginseng, ranked fifth, and its MeanDecreaseGini value was 2.28. The experimental results showed that the B2C2 treatment had the best inhibitory effect on Fusarium, and the relative abundance of Fusarium in Panax notoginseng rhizosphere soil decreased by 86.79% under B2C2 treatment; the B1C2 treatment had the best inhibitory effect on Ilyonectria, and the relative abundance of Ilyonectria in the Panax notoginseng rhizosphere soil decreased by 93.60% under B1C2 treatment. Therefore, if we want to improve the soil with acute Ralstonia solanacearum root rot, we should use the B2C2 treatment to improve the soil environment; if we want to improve the soil with yellow rot disease, we should use the B1C2 treatment to improve the soil environment.
Recent studies have revealed that PTPRZ1-MET (ZM) fusion plays a pivotal role in the progression of glioma to glioblastoma multiforme (GBM), thus serving as a biomarker to distinguish between primary GBM and secondary GBM (sGBM). However, the mechanisms through which ZM fusion influences this progression remain to be elucidated. GBMs with ZM showed poorer prognoses and greater infiltration of tumor-associated macrophages (TAMs) than those without ZM. Glioma stem-like cells (GSCs) and TAMs play complex roles in glioma recurrence, glioma progression and therapy resistance. In this study, we analyzed RNA-seq data from sGBM patients' glioma tissues with or without ZM fusion, and found that stemness and macrophage markers were more highly expressed in sGBM patients harboring ZM than in those without ZM fusion. ZM enhanced the self-renewal and proliferation of GSCs, thereby accelerating glioma progression. In addition, ZM-positive GSCs facilitated the infiltration of TAMs and drove their polarization toward an immunosuppressive phenotype, which was primarily accomplished through the extracellular secretion of ISG20. Our research identified the MET-STAT3-ISG20 axis within GSCs, thus demonstrating the critical role of ZM in GBM initiation and progression. Our study demonstrated that, in contrast to ZM-positive differentiated glioma cells, ZM-positive GSCs upregulated ISG20 expression through the MET-STAT3-ISG20 axis. The extracellular secretion of ISG20 recruited and induced M2-like polarization in macrophages, thereby promoting tumor progression. Our results reveal a novel mechanism involved in ZM-positive GBM pathogenesis and identify potential therapeutic targets.
Bromophenols (BPs) are a class of ubiquitous emerging halogenated pollutants. Their 19 congeners are problematically separated and detected. This work described the separation and detection of 19 BP congeners by gas chromatography-mass spectrometry (GC-MS). Investigations into the derivatization of bromophenols were carried out using two silylation reagents (N,O-bis(trimethylsilyl)trifluoroacetamide and N-methyl-N-(trimethylsily)trifluoroacetamide), two alkylation reagents (methyl iodide and trimethylsilyldiazomethane) and acetic anhydride prior to GC-MS analysis. Optimal chromatographic separation, sensitivity, and linearity were achieved after BP derivatization using acetic anhydride, featuring the equipment detection limits of 0.39-1.26 pg and correlation coefficients of 0.9948-0.9999 (linear range: 0.5-250 ng mL-1) for all 19 BP congeners. Furthermore, the simultaneous determination of 19 bromophenols and 19 bromoanisoles, common environmental transformation products of BPs, is also demonstrated. The improved analytical performance on GC-MS after derivatization would benefit investigations on the environmental origins, behaviors and fates of BPs and their environmental metabolites.
The gecko can achieve flexible climbing on various vertical walls and even ceilings, which is closely related to its unique foot adhesion system. In the past two decades, the mechanism of the gecko adhesion system has been studied in-depth, and a verity of gecko-inspired adhesives have been proposed. In addition to its strong adhesion, its easy detachment is also the key to achieving efficient climbing locomotion for geckos. A similar controllable adhesion characteristic is also key to the research into artificial gecko-inspired adhesives. In this paper, the structures, fabrication methods, and applications of gecko-inspired controllable adhesives are summarized for future reference in adhesive development. Firstly, the controllable adhesion mechanism of geckos is introduced. Then, the control mechanism, adhesion performance, and preparation methods of gecko-inspired controllable adhesives are described. Subsequently, various successful applications of gecko-inspired controllable adhesives are presented. Finally, future challenges and opportunities to develop gecko-inspired controllable adhesive are presented.
BACKGROUND: The efficacy of surgical intervention in ameliorating long-term prognosis for moderate volume of cerebral hemorrhage in the thalamus-internal capsule region remains unsubstantiated by clinical investigations. Consequently, the acquisition of credible evidence is imperative to authenticate the effectiveness of these methodologies. METHODS: One hundred and three eligible patients with moderate-volume thalamus-internal capsule region cerebral hemorrhage. Twenty-seven pairs of successful matches after using the 1:1 propensity score matching method, totaling 54 patients, were analyzed. The short- and long-term treatment outcomes of patients in the stereotactic surgery and conservative treatment groups were compared. The prognosis of the 2 groups of patients was analyzed by logistic regression analysis and model comparison. RESULTS: The primary outcome of this study was to assess the assessment of daily living scores after 6 months of treatment. Based on the analysis of this study, the assessment of daily living of the surgical group were significantly higher than those of the conservative treatment group after 6 months of treatment (P < 0.001), and the difference was statistically significant. The amount of residual hematoma was significantly lower in the stereotactic surgery group than in the conservative treatment group at 3 days, 7 days, and 2 weeks after the onset of the disease (P < 0.001), and the complication rate was lower than the conservative treatment group (P < 0.05). Univariate logistic regression showed that the risk of severe neurological dysfunction for patients in the surgery group was (odds ratio -0.27, 95% confidence interval: 0.08-0.86, P < 0.05). In multivariate logistic regression analysis, the odds ratio was 0.29 (95% confidence interval: 0.09-0.96, P < 0.05) after adjusting for all covariates. CONCLUSIONS: For moderate-volume thalamus-internal capsule region cerebral hemorrhage, stereotactic paracentesis has the advantage of a shorter hospital stay and a lower complication rate than conservative treatment. Moreover, it yields superior outcomes in terms of daily living assessment scores after six months of treatment and enhanced neurological recovery.
Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and antiviral responses through the ubiquitination of protein targets. TRIM21 was reported to be related to the imbalance of host cell homeostasis caused by viral infection. Our studies indicated that H5N1 highly pathogenic avian influenza virus (HPAIV) infection up-regulated TRIM21 expression in A549 cells. Western blot and qPCR results showed that knockdown of TRIM21 alleviated oxidative stress and ferroptosis induced by H5N1 HPAIV and promoted the activation of antioxidant pathways. Co-IP results showed that TRIM21 promoted oxidative stress and ferroptosis by regulating the SQSTM1-NRF2-KEAP1 axis by increasing SQSTM1 K63-linked polyubiquitination under the condition of HPAIV infection. In addition, TRIM21 attenuated the inhibitory effect of antioxidant NAC on HPAIV titers and enhanced the promoting effect of ferroptosis agonist Erastin on HPAIV titers. Our findings provide new insight into the role of TRIM21 in oxidative stress and ferroptosis induced by viral infection.
Ferroptosis , Influenza A Virus, H5N1 Subtype , Influenza in Birds , Animals , Humans , Antioxidants/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism
Shear thickening of multimodal suspensions has proven difficult to understand because the rheology depends largely on the microscopic details of stress-induced frictional contacts at different particle size distributions (PSDs). Our discrete particle simulations below a critical volume fraction Ïc over a broad range of shear rates and PSDs elucidate the basic mechanism of order-disorder transition. Around the theoretical optimal PSD (relative content of small particles ζ1= 0.26), particles order into a layered structure in the Newtonian regime. At the onset of shear thickening, this layered structure transforms to a disordered one, accompanied by an abrupt viscosity jump. Minor increase in large-large particle contacts after the order-disorder transition causes apparent increase in radial force along the compressional axis. Bidisperse suspensions with less regular but stable layered structure at ζ1= 0.50 show good fluidity in the shear thickening regime. This work shows that in inertial flows where particle collisions dominate, order-disorder transition could play an essential role in shear thickening for bidisperse suspensions.
Naturally aged microplastics (NAMPs) and arsenic (As) have been reported to coexist in and threaten potentially to soil-plant ecosystem. The research explored the combined toxic effects of NAMPs and As to lettuce (Lactuca sativa L.) growth, and the distribution, accumulation and bioavailability of As in soil aggregates. The As contaminated soil with low, medium and high concentrations (L-As, M-As, H-As) were treated with or without NAMPs, and a total of six treatments. The results displayed that, in comparison to separate treatments of L-As and M-As, the presence of NAMPs increased the total biomass of lettuce grown at these two As concentrations by 68.9 % and 55.4 %, respectively. Simultaneous exposure of NAMPs and L-As or M-As led to a decrease in As content in shoot (0.45-2.17 mg kg-1) and root (5.68-14.66 mg kg-1) of lettuce, indicating an antagonistic effect between them. In contrast, co-exposure to H-As and NAMPs showed synergistic toxicity, and the leaf chlorophyll and nutritional quality of lettuce were also reduced. NAMPs altered the ratio of different soil aggregate fractions and the distribution of bioavailable As within them, which influenced the absorption of As by lettuce. In conclusion, these direct observations assist us in enhancing the comprehend of the As migration and enrichment characteristics in soil-plant system under the influence of NAMPs.
Arsenic , Soil Pollutants , Arsenic/analysis , Lactuca , Microplastics , Plastics , Soil , Biological Availability , Ecosystem , Soil Pollutants/analysis
OBJECTIVE: IDH-mutant grade 4 astrocytomas (AIDHmut/G4) are divided into primary de novo (pAIDHmut/G4) and secondary with a history of prior lower-grade gliomas (LGGs; sAIDHmut/G4). The mutational spectrum and DNA methylation patterns are homogeneous within de novo pAIDHmut/G4 and evolved sAIDHmut/G4, but the two groups have different diagnoses, management, and outcomes. This study sought to systematically compare the clinical, pathological, and survival characteristics between them. METHODS: Of the 871 grade 4 astrocytomas with data for IDH mutation, 698 (80.1%) were primary and 173 (19.9%) were secondary. Of the 698 primary tumors, 103 (14.8%) were pAIDHmut/G4, and of the 173 secondary tumors, 108 (62.4%) were sAIDHmut/G4. Clinical, pathological, and survival features were compared between pAIDHmut/G4 and sAIDHmut/G4. Multivariate analyses were performed to identify prognostic factors. RESULTS: Patients with sAIDHmut/G4 had significantly shorter median overall survival (OS; 11.8 vs 34.2 months, hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.367-5.306, p = 0.004) and progression-free survival (PFS; 8.5 vs 24.3 months, HR 2.83, 95% CI 1.532-5.235, p = 0.001) than patients with pAIDHmut/G4. In patients with sAIDHmut/G4, resection status and chemotherapy were independent prognostic factors for OS and PFS; in patients with pAIDHmut/G4, LGG component, resection status, and O6-methylguanine DNA methyltransferase promoter methylation were independent prognostic factors. The therapeutic strategies of LGGs did not influence survival of patients with sAIDHmut/G4, but patients who had not received radiotherapy or chemotherapy when they were diagnosed with LGGs were found to benefit from radiotherapy or chemotherapy when they progressed to sAIDHmut/G4. CONCLUSIONS: The different clinical characteristics, survival, and risk factors between sAIDHmut/G4 and pAIDHmut/G4 provide a reference to guide treatment decisions in AIDHmut/G4.
Astrocytoma , Brain Neoplasms , Glioblastoma , Glioma , Humans , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Glioma/pathology , Progression-Free Survival , DNA Methylation/genetics , Glioblastoma/genetics , Isocitrate Dehydrogenase/genetics , Astrocytoma/genetics , Astrocytoma/therapy , Mutation/genetics
Background: This study aimed to evaluate the association between the glucose-to-lymphocyte ratio (GLR) and all-cause mortality in intensive care unit (ICU) patients with Non-traumatic cerebral hemorrhage. Methods: This is a retrospective cohort study. Baseline data and in-hospital prognosis from patients with non-traumatic cerebral hemorrhage admitted to the intensive care unit. Multivariate COX regression analysis was applied and adjusted hazard ratios (HR) and 95% predictive values with confidence intervals (CI) were calculated. Survival curves for the two groups of cases were plotted using K-M curves, and subgroup analyses were performed in one step. Using restricted cubic spline curves, we analyzed the potential linear relationship between GLR and outcome indicators. Results: In the Medical Information Mart for Intensive Care IV (MIMIC-IV database), we extracted 3,783 patients with nontraumatic intracerebral hemorrhage, and 1,806 patients were finally enrolled in the study after exclusion of missing values and patients with a short hospital stay. The overall ICU mortality rate was 8.2% (148/1806) and the in-hospital mortality rate was 12.5% (225/1806). The use of curve fitting yielded a significant linear relationship between GLR and both ICU mortality and in-hospital mortality. It also suggested a reference point at GLR=3.9. These patients were categorized into high and low subgroups based on the median value of their GLR (GLR = 3.9). Model comparisons based on multivariate COX regression analysis showed that in-hospital mortality was higher in the high GLR group after adjusting for all confounders (HR = 1.31, 95% CI: 1.04-1.47), while the ICU mortality in the high GLR group was (HR = 1.73, 95% CI: 1.18-2.52). Stratified analyses based on age, gender, race, GCS, BMI, and disease type showed stable correlations between the high GLR group and in-hospital and ICU mortality. Conclusion: Based on our retrospective analysis, it is known that as the GLR increased, the in-hospital mortality rate and ICU mortality rate of patients with nontraumatic cerebral hemorrhage also increased progressively in the United States in a clear linear relationship. However, further studies are needed to confirm these findings.
Blood Glucose , Hyperglycemia , Humans , Retrospective Studies , Lymphocytes , Glucose , Cerebral Hemorrhage
The photon spectrum from free-electron laser (FEL) light sources offers valuable information in time-resolved experiments and machine optimization in the spectral and temporal domains. We have developed a compact single-shot photon spectrometer to diagnose soft X-ray spectra. The spectrometer consists of an array of off-axis Fresnel zone plates (FZP) that act as transmission-imaging gratings, a Ce:YAG scintillator, and a microscope objective to image the scintillation target onto a two-dimensional imaging detector. This spectrometer operates in segmented energy ranges which covers tens of electronvolts for each absorption edge associated with several atomic constituents: carbon, nitrogen, oxygen, and neon. The spectrometer's performance is demonstrated at a repetition rate of 120â Hz, but our detection scheme can be easily extended to 200 kHz spectral collection by employing a fast complementary metal oxide semiconductor (CMOS) line-scan camera to detect the light from the scintillator. This compact photon spectrometer provides an opportunity for monitoring the spectrum downstream of an endstation in a limited space environment with sub-electronvolt energy resolution.
Microbial reduction plays a crucial role in Hg redox and the global cycle. Although intracellular Hg(II) reduction mediated by MerA protein is well documented, it is still unclear whether or how bacteria reduce Hg(II) extracellularly without its internalization. Herein, for the first time, we discovered the extracellular reduction of Hg(II) by a widely distributed aerobic marine bacterium Alteromonas sp. KD01 through a superoxide-dependent mechanism. The generation of superoxide by Alteromonas sp. KD01 was determined using 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide and methyl cypridina luciferin analogue as probes via UV-vis and chemiluminescence detection, respectively. The results demonstrated that Hg(II) reduction was inhibited by superoxide scavengers (superoxide dismutase (SOD) and Cu(NO3)2) or inhibitors of reduced nicotinamide adenine dinucleotide (NADH) oxidoreductases. In contrast, the addition of NADH significantly improved superoxide generation and, in turn, Hg(II) reduction. Direct evidence of superoxide-mediated Hg(II) reduction was provided by the addition of superoxide using KO2 in deionized water and seawater. Moreover, we observed that even superoxide at an environmental concentration of 9.6 ± 0.5 nM from Alteromonas sp. KD01 (5.4 × 106 cells mL-1) was capable of significantly reducing Hg(II). Our findings provide a greater understanding of Hg(II) reduction by superoxide from heterotrophic bacteria and eukaryotic phytoplankton in diverse aerobic environments, including surface water, sediment, and soil.
Alteromonas , Mercury , Superoxides/metabolism , Alteromonas/metabolism , NAD/metabolism , Bacteria/metabolism , Water
BACKGROUND: Coronary heart disease (CHD) is a major complication of type 2 diabetes mellitus (T2DM), which causes an adverse prognosis. There is an urgent need to explore effective biomarkers to evaluate the patients' adverse outcomes. OBJECTIVE: This study aimed to identify a novel indicator for screening T2DM and T2DM-CHD and predicting adverse prognosis. MATERIALS AND METHODS: The study enrolled 52 healthy individuals, 85 T2DM patients, and 97 T2DM patients combined with CHD. Serum miR-199-3p levels in all study subjects were detected with PCR, and its diagnostic significance was evaluated by receiver operating curve (ROC) analysis. The involvement of miR-199-3p in disease development was assessed by the Chi-square test, and the logistic regression analysis was performed to estimate the risk factor for major adverse cardiovascular events (MACE) in T2DM-CHD patients. RESULTS: Significant downregulation of miR-199-3p was observed in the serum of both T2DM and T2DM-CHD patients, which discriminated patients from healthy individuals and distinguished T2DM and T2DM-CHD patients. Reduced serum miR-199-3p was associated with the increasing blood glucose, glycated hemoglobin (HbA1c), and homeostasis model assessment-insulin resistance index (HOMA-IR) of T2DM patients and the increasing triglycerides (TG), low-density lipoprotein (LDL), fibrinogen, and total cholesterol (TC) and decreasing high-density lipoprotein (HDL) of T2DM-CHD patients. miR-199-3p was also identified as a biomarker predicting the occurrence of MACE. CONCLUSION: Downregulated miR-199-3p could screen the onset of T2DM and its complication with CHD. Reduced serum miR-199-3p was associated with the severe development of T2DM and T2DM-CHD and predicted the adverse outcomes of T2DM-CHD patients.
Cardiovascular Diseases , Coronary Disease , Diabetes Mellitus, Type 2 , MicroRNAs , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Risk Factors , Biomarkers , MicroRNAs/genetics , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Coronary Disease/genetics , Cardiovascular Diseases/complications
Knowledge of x-ray free electron lasers' (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs' self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator's configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties.
Natural organic matter (NOM) exhibits a distinctive electron-donating capacity (EDC) that serves a pivotal role in the redox reactions of contaminants and minerals through the transformation of electron-donating phenolic moieties. However, the ambiguity of the molecular transformation pathways (MTPs) that engender the EDC during NOM oxidation remains a significant issue. Here, MTPs that contribute to EDC were investigated by identifying the oxidized products of phenolic model compounds and NOM samples in direct or mediated electrochemical oxidation (DEO or MEO, respectively) using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). It was found that the oxidation of newly formed phenolic-OH (ArOH) and the oxidative coupling reaction of the phenoxy radical are the main MTPs that directly contribute to EDC, in addition to the transformation of hydroquinones to quinones. Notably, the oxidative coupling reaction of ArOH contributed at least 22-42% to the EDC. Ferulic acid-like structures can also directly contribute to EDC by incorporating H2O into their acrylic substituents. Furthermore, the opening of C rings can indirectly attenuate the EDC through structural alterations in the electron-donating process of NOM. Decarboxylation can either weaken or enhance the EDC depending on the structure of the phenolic moieties in NOM. These findings suggest that the EDC of NOM is a comprehensive result of multiple NOM MTPs, involving not only ArOH oxidation but also the addition of H2O to olefinic bonds and bond-breaking reactions. Our work provides molecular evidence that aids in the comprehension of the multiple EDC-associated transformation pathways of NOM.
Electrons , Oxidation-Reduction , Mass Spectrometry
The incidence and mortality rate of gastric cancer (GC) have remained high worldwide. Although some progress has been made in immunotargeted therapy, the treatment effect remains limited. With more attention has been paid to the immune potential of tumor-associated macrophages (TAMs), but the specific mechanisms of tumor immunity are still unclear. Thus, we screened marker genes in TAMs differentiation (MDMs) through single-cell RNA sequencing, and combined with GC transcriptome data from TCGA and GEO databases, the clinical and TME characteristics, prognostic differences, immune infiltration, and drug sensitivity among different subtypes of patients with GC in different data sets were analyzed. A prognostic model of GC was constructed to evaluate the prognosis and immunotherapy response of patients with GC. In this study, we extensively studied the mutations in MDMs such as CGN, S100A6, and C1QA, and found differences in the infiltration of immune cells and immune checkpoints including M2 TAMs, T cells, CD274, and CTLA4 in different GC subtypes. In the model, we constructed a predictive scoring system with high accuracy and screened out key MDMs-related genes associated with prognosis and M2 TAMs, among which VKORC1 may be involved in GC progression and iron death in tumor cells. Therefore, this study explores the therapeutic strategy of TAMs reprogramming in-depth, providing new ideas for the clinical diagnosis, treatment, and prognosis assessment of GC.
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Tumor Microenvironment/genetics , Multiomics , Tumor-Associated Macrophages , Immunotherapy , Prognosis , Vitamin K Epoxide Reductases
Mercury sulfide nanoparticles (HgSNPs), which occur widely in oxic and anoxic environments, can be microbially converted to highly toxic methylmercury or volatile elemental mercury, but it remains challenging to assess their bioavailability. In this study, an Escherichia coli-based whole-cell fluorescent biosensor was developed to explore the bioavailability and microbial activation process of HgSNPs. Results show that HgSNPs (3.17 ± 0.96 nm) trigger a sharp increase in fluorescence intensity of the biosensor, with signal responses almost equal to that of ionic Hg (Hg(II)) within 10 h, indicating high bioavailability of HgSNP. The intracellular total Hg (THg) of cells exposed to HgSNPs (200 µg L-1) was 3.52-8.59-folds higher than that of cells exposed to Hg(II) (200 µg L-1), suggesting that intracellular HgSNPs were only partially dissolved. Speciation analysis using size-exclusion chromatography (SEC)-inductively coupled plasma mass spectrometry (ICP-MS) revealed that the bacterial filtrate was not responsible for HgSNP dissolution, suggesting that HgSNPs entered cells in nanoparticle form. Combined with fluorescence intensity and intracellular THg analysis, the intracellular HgSNP dissolution ratio was estimated at 22-29%. Overall, our findings highlight the rapid internalization and high intracellular dissolution ratio of HgSNPs by E. coli, and intracellular THg combined with biosensors could provide innovative tools to explore the microbial uptake and dissolution of HgSNPs.
